In health, the liver orchestrates the metabolism of
proteins and
amino acids. When the liver is diseased, the regulation of
protein metabolism is frequently disturbed. The manifestations of disturbed
protein metabolism in
liver disease are varied and change with disease aetiology and severity. The hallmarks of
protein and
amino acid metabolism in
liver disease are lowered concentrations of circulating branched-chain and increased concentrations of circulating
aromatic amino acids with concomitantly altered
amino acid kinetics. The changes in
amino acid kinetics in
liver disease are characterized by increased endogenous
leucine flux, an
indicator of
protein breakdown, and
leucine oxidation in the post-absorptive state (when calculated using a reciprocal-pool model and normalized for body cell mass). In addition, the increase in whole-body
protein synthesis in response to an
amino acid infusion may be attenuated in patients with
cirrhosis. These changes are often accompanied by clinically apparent muscle wasting, manifest as
protein-calorie malnutrition, and associated low levels of hepatically synthesized
plasma proteins. While the pathogenesis of these changes in
protein and
amino acid metabolism has not been elucidated, altered levels of circulating
hormones, known to affect
protein metabolism, are probably important. Lowered levels of
micronutrients and trace metals and elevated levels of
cytokines may also play a role.